Ranitidine upon meal-induced gastric secretion: oral pharmacokinetics and plasma concentration effect relationships.

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Abstract
Ranitidine oral kinetics and plasma concentration-effect relationships upon meal-induced gastric secretion were investigated in normal subjects. Four oral doses of ranitidine (50, 100, 150 or 200 mg) and placebo were tested. Oral ranitidine showed a terminal half-life of .apprx. 2 h 25 min. Maximal plasma level was .apprx. 240 ng/ml for a 100-mg dose and occurred .apprx. 1 h after dose. From the range of 50 to 200 mg dose, no indication of nonlinearity was observed in the drug kinetics. Ranitidine administration resulted in a dose-related reduction in meal-stimulated acid secretion, reaching 46, 70, 82 and 92%, respectively. Mean ranitidine plasma concentrations producing 50 and 80% inhibition of acid secretion were 73 and 180 ng/ml, respectively, with great interindividual variability. Ranitidine oral doses 150 and 200 mg maintained IC50 [median inhibitory concentration] for at least 4.5 and 5.5 h, respectively. Upon oral administration, ranitidine exerted no effect on gastric emptying of the meal but slightly decreased the gastrin response to the meal.